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Trends in obesity and glucagon‐like peptide‐1 receptor agonist prescriptions in type 1 diabetes in the United States

Abstract
Aims
To characterize trends in obesity and prescriptions for glucagon-like peptide-1 receptor agonists (GLP-1RAs) across body mass index (BMI) categories among US youth and adults with type 1 diabetes (T1D) from 2008 to 2023.
Materials and Methods
Patients with T1D were identified using a validated algorithm using de-identified electronic health record (EHRs) data from 33 US health systems. BMI categories were based on age- and sex-specific percentiles for youth (2–19 years) and World Health Organization cut points for adults (≥20 years). Trends in obesity and GLP1-RA prescriptions were characterized by BMI categories among youth and adults with T1D from 2008–2011 to 2020–2023.
Results
From 2008–2011 to 2020–2023, the prevalence of obesity among youth with T1D increased from 18.1% (95% confidence interval [CI], 17.3%–18.9%) to 26.0% (25.2%–26.8%) (p-for-trend < 0.001). Among adults with T1D, the prevalence of obesity rose from 30.5% (30.0%–31.0%) in 2008–2011 to 38.1% (37.8%–38.5%) in 2020–2023 (p-for-trend < 0.001). Obesity was highest in Black and Hispanic youth and adults, and racial and ethnic disparities persisted over time. Over the last 15-year period, GLP-1RA prescriptions significantly increased across all BMI categories in a dose–response manner among both youth and adults with T1D (all p-for-trend < 0.001).
Conclusions
Over the last 15-year period, obesity has reached epidemic levels in US youth and adults with T1D, with significant disparities among racial and ethnic minoritized populations. These findings, coupled with the increase in GLP-1RA prescriptions, underscore the urgent need for data on GLP-1RAs' safety and effectiveness and guidance for obesity management in T1D.

A systematic literature review on the burden of diabetic ketoacidosis in type 2 diabetes mellitus

Abstract
Aim
To understand the existing literature on the epidemiology and clinical, humanistic, and economic burden of diabetic ketoacidosis (DKA) in people living with type 2 diabetes mellitus (T2DM).
Materials and Methods
MEDLINE, Embase and the Cochrane library were systematically searched for studies published between 1 January 2014 and 14 December 2023. Clinical trials and observational studies, conducted in people living with T2DM, were included if they provided data on DKA epidemiology, morbidity, mortality, hospitalizations or patient-reported outcomes. Studies of DKA-associated costs in T2DM were also included. Data were summarized descriptively.
Results
Overall, 197 publications were included. We found wide variations in DKA prevalence (0.0%–50.0%; 5th–95th percentile: 0.02%–26%; 126 publications) and incidence (0.0–24.5 events per 1000 patient years; 5th–95th percentile: 0.004–7.6 events per 1000 patient years; 37 publications). Populations at increased risk of DKA included patients using sodium–glucose cotransporter-2 inhibitors, those using insulin and those with poor glycaemic control. The most common precipitating factors were infection and non-adherence to treatment. There was limited evidence on the humanistic burden of DKA, but the results highlighted a high burden of complications including acute kidney injury or failure. The length of hospital stay ranged from days to several weeks.
Conclusions
DKA is associated with a high clinical burden in people living with T2DM. Resources to screen for and potentially prevent DKA may reduce the burden of DKA for patients with T2DM and the healthcare system.

The safety, tolerability, pharmacokinetics and pharmacodynamics of GZR18 in healthy American and Chinese adult subjects

Abstract
Aims
GZR18, a novel long-acting GLP-1 receptor agonist, has demonstrated substantial metabolic improvements in diabetic and obese animal models. The present studies aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the ascending dose of GZR18 in healthy American and Chinese subjects.
Materials and Methods
In these phases 1, randomized, double-blind, placebo-controlled, sequential, dose-escalation US and Chinese studies, healthy American and Chinese adults with similar age were enrolled to once-weekly subcutaneous injection of GZR18 or placebo. The studies included three cohorts of male American subjects (cohorts US-1–3) and six cohorts of Chinese subjects (cohorts CN-1–6, male and female), each with a specified target dose of GZR18 ranging from 1 to 50 μg/kg (1–10 μg/kg for US study and 5–50 μg/kg for Chinese study). The primary endpoints were the safety and tolerability of GZR18. Blood samples were collected for PK and PD analysis of GZR18 before and after dosing. A population PK analysis of GZR18 was conducted to ascertain whether there are ethnic PK differences between American and Chinese adults.
Results
The exposure of GZR18 was comparable between healthy American and Chinese subjects, with the geometric mean ratio between the two populations for AUC0-t and C
max close to 1. A dose-dependent increase in AUC0–t and C
max occurred in both populations. The median time to maximum plasma concentrations (T
max) in American subjects ranged from 72 to 96 h, and the mean T
max ranged from 60 to 72 h in Chinese subjects. The half-life of GZR18 was approximately 7 days in both American and Chinese subjects. Evident body weight reduction was observed in GZR18 treatment groups in Chinese subjects (cohorts CN-3–6 on Day 15, −1.25 to −1.86 kg; −1.88% to −3.11%). No deaths, serious adverse events or hypoglycaemia were reported. Decreased appetite and nausea were the most frequently reported treatment-emergent adverse events, observed in Chinese study and mild in severity. The safety profile of GZR18 was generally consistent with the same class of drugs.
Conclusions
GZR18 demonstrates good tolerability in healthy American and Chinese subjects. No ethnic differences were observed between healthy American and Chinese subjects. The safety, PK and PD profiles of GZR18 support its further clinical evaluation for glycaemic and body weight control.